Epilepsy, a neurological disorder characterized by the occurrence of seizures (specifically episodic impairment or loss of consciousness, abnormal motor phenomena, psychic or sensory disturbances, or the perturbation of the autonomic nervous system), is debilitating to a great number of people. It is believed that as many as two to four million Americans may suffer from various forms of epilepsy. Research has found that its prevalence may be even greater worldwide, particularly in less economically developed nations, suggesting that the worldwide figure for epilepsy sufferers may be in excess of one hundred million.
Because epilepsy is characterized by seizures, its sufferers are frequently limited in the kinds of activities they may participate in. Epilepsy can prevent people from driving, working, or otherwise participating in much of what society has to offer. Some epilepsy sufferers have serious seizures so frequently that they are effectively incapacitated.
Furthermore, epilepsy is often progressive and can be associated with degenerative disorders and conditions. Over time, epileptic seizures often become more frequent and more serious, and in particularly severe cases, are likely to lead to deterioration of other brain functions (including cognitive function) as well as physical impairments.
Electrical stimulation is an emerging therapy for epilepsy, and responsive therapy (i.e., therapy that is applied only when a device determines it is necessary or advantageous to do so) is at the cutting edge of electrical stimulation therapy.
Currently approved and available electrical stimulation devices apply continuous electrical stimulation to neural tissue surrounding or near implanted electrodes, and do not perform any detection—they are not responsive to relevant neurological conditions.
The NeuroCybemetic Prosthesis (NCP) from Cyberonics, for example, applies continuous electrical stimulation to the patient's vagus nerve. This approach has been found to reduce seizures by about 50% in about 50% of patients. Unfortunately, a much greater reduction in the incidence of seizures is needed to provide substantial clinical benefit.
The Activa device from Medtronic is a pectorally implanted continuous deep brain stimulator intended primarily to treat Parkinson's disease. In operation, it supplies a continuous electrical pulse stream to a selected deep brain structure where an electrode has been implanted. Continuous stimulation of deep brain structures for the treatment of epilepsy has not met with consistent success. To be effective in terminating seizures, it is believed that one effective site where stimulation should be performed is near the focus of the epileptogenic region. The focus is often in the neocortex, where continuous stimulation may cause significant neurological deficit with clinical symptoms including loss of speech, sensory disorders, or involuntary motion. Accordingly, research has been directed toward automatic responsive epilepsy treatment based on a detection of imminent seizure.
A typical epilepsy patient experiences episodic attacks or seizures, which are generally electrographically defined as periods of abnormal neurological activity. As is traditional in the art, such periods shall be referred to herein as “ictal”. In many patients these ictal periods tend to cluster or occur in groups; at and around those times a patient is particularly prone to experience a seizure.
Seizure clusters are undesired for a number of reasons. Nearly all seizures, whether they involve loss of motor control, involuntary movements, or lapses of consciousness, are dangerous (both in a direct clinical sense and also as a result of accidents). Moreover, epilepsy is generally regarded as somewhat progressive, in that seizures tend to damage and degenerate already dysfunctional brain tissue. Seizure clusters may represent a particularly dysfunctional brain state, and when responsive therapy fails to adequately treat a patient, the progression of the disease may continue and the patient may be incapacitated over a particularly long period of time. This is true even if clinical symptoms are not evident.
Most work on the detection and responsive treatment of seizures via electrical stimulation has focused on analysis of electroencephalogram (EEG) and electrocorticogram (ECoG) waveforms. In common usage, the term “EEG” is often used to refer to signals representing aggregate neuronal activity potentials detectable via electrodes applied to a patient's scalp, though the term can also refer to signals obtained from deep in the patient's brain via depth electrodes and the like. Specifically, “ECoGs” refer to signals obtained from internal electrodes near the surface of the brain (generally on or under the dura mater); an ECoG is a particular type of EEG. Unless the context clearly and expressly indicates otherwise, the term “EEG” shall be used generically herein to refer to both EEG and ECoG signals, regardless of where in the patient's brain the electrodes are located.
It is best for a patient to avoid seizures entirely, but if that is not possible, it is generally preferable to be able to detect and treat a seizure at or near its beginning, or even before it begins. The beginning of a seizure is referred to herein as an “onset.” However, it is important to note that there are two general varieties of seizure onsets. A “clinical onset” represents the beginning of a seizure as manifested through observable clinical symptoms, such as involuntary muscle movements or neurophysiological effects such as lack of responsiveness. An “electrographic onset” refers to the beginning of detectable electrographic activity indicative of a seizure. An electrographic onset will frequently occur before the corresponding clinical onset, enabling intervention before the patient suffers symptoms, but that is not always the case. In addition, there are changes in the EEG that occur seconds or even minutes before the electrographic onset that can be identified and used to facilitate intervention before electrographic or clinical onsets occur. This capability would be considered seizure prediction, in contrast to the detection of a seizure or its onset.
U.S. Pat. No. 6,016,449 to Fischell, et al., for System for Treating Neurological Disorders (which is hereby incorporated by reference as though set forth in full herein), describes an implantable seizure detection and treatment system. In the Fischell system, various detection methods are possible, all of which essentially rely upon the analysis (either in the time domain or the frequency domain) of processed EEG signals. Fischell's controller is preferably implanted intracranially, but other approaches are also possible, including the use of an external controller. The processing and detection techniques applied in Fischell are generally well suited for implantable use. When a seizure is detected, the Fischell system applies responsive electrical stimulation to terminate the seizure, a capability that will be discussed in further detail below.
A more recent embodiment of seizure detecting device is described and claimed in U.S. Pat. No. 6,810,285 to Pless et al., also incorporated by reference as though set forth in full.
As is well known, it has been suggested that it is possible to treat and terminate seizures by applying electrical stimulation to the brain. See, e.g., U.S. Pat. No. 6,016,449 to Fischell et al., and H. R. Wagner, et al., Suppression of cortical epileptiform activity by generalized and localized ECoG desynchronization, Electroencephalogr. Clin. Neurophysiol. 1975; 39(5): 499-506. And it is postulated that a “stimulate early and often” strategy is advantageous. Observed epileptiform activity, even if it does not result in clinical symptoms, may be a subclinical seizure. Treatment of such subclinical activity may reduce overall seizure rates and reduce the brain's tendency to produce such activity in the future. In any event, reasonable quantities of “excess” stimulation have not been found to be disadvantageous.
Even when detection is operating effectively and an implantable system provides electrical stimulation therapy in response to electrographic events, and despite the suppression of those individual events, there may be times when the patient's brain is in a state of enhanced excitability and the rate of electrographic events increases. A responsive device, even when it is capable of applying therapy in response to individual electrographic events, might not be successful in keeping all of them from progressing to clinical seizures. Accordingly, it would be advantageous to have an implantable system for treating epilepsy that is capable of observing and responding to periods of increased activity and increased excitability, which is often manifested by a period of high therapy density (the system treats multiple electrographic events in succession, yet they continue to occur). When a period of increased therapy activity is observed, it would be advantageous to be able to warn the patient to take protective measures or take an increased dose of an anticonvulsant medication or to automatically provide additional therapy (above and beyond the responsive therapy already being applied) to reduce the impact or likelihood of a clinical seizure.
As is well known in the art, the computational ability of a processor-controlled system is directly related to both size and power consumption. In accordance with the above considerations, therefore, it would be advantageous to have sufficient detection and prediction capabilities to avoid a substantial number of false positive and false negative detections, and yet consume little enough power (in conjunction with the other subsystems) to enable long battery life. Such an implantable device would have a relatively low-power central processing unit to reduce the electrical power consumed by that portion.
As noted above, it has been observed that despite a high frequency of successful stimulations of electrographic events, there may be times when the numbers of electrographic events continues to increase resulting in an increased risk of a breakthrough seizure. This is true regardless of whether seizures are being treated with electrical stimulation as described above, and regardless of whether such treatments are successful on an individual basis (i.e. clinical symptoms are avoided). These observations suggest that there are times that can be identified by an increase in the amount of responsive stimulation delivered, when the patient's brain is highly excitable and conditions are particularly conducive to a seizure breakthrough. At these times, a patient's health and well-being may be particularly at risk.
At the current time, there is no known implantable device that is capable of detecting and responding to neurophysiological conditions suggestive of increased excitability and the possibility of a breakthrough seizure, or providing warnings or additional actions in response to a sequence of therapies having been applied.